Diabetes Complications

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

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**1. Introduction**

**Chapter 7**

**Abstract**

Diabetes Microvascular

Epigenetic Modifications

*Neerja Aggarwal and Pawan Kumar Kare*

Complications: An Overview of

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are two serious and long-standing microvascular complications of type 2 diabetes mellitus (T2DM) whose burden is increasing worldwide due to increasing burden of T2DM. Several factors which may predispose to the development of DN and DR are persistent hyperglycemia and its consequences such as formation of advanced glycation end products (AGEs), activation of hexosamine pathway, polyol pathway, uncontrolled blood pressure, increased oxidative stress, age, family history of kidney disease or hypertension, ethnic background etc. However, the pathophysiological mechanisms of these complications are complicated and not completely understood yet. Hence it is the demand to discover newer approaches to treat these devastating complications completely. Recently, various epigenetic modifications, which are the transmissible alterations in the expressions of a gene, are being studied to understand the pathophysiology of diabetic vascular complications. Metabolic and environmental factors may lead to dysregulated epigenetic mechanisms which might further affect the chromatin structure and related expressions of a gene, which may lead to diabetes-associated complications. Therefore, it is the need to explore its role in vascular complications in the current scenario. In this chapter, various epigenetic studies with regard to DN and DR, epigenome-wide association studies (EWAS) approach, and starting clinical material for such studies have been discussed. We have also summarized the better understanding of epigenetic alterations and their role in microvascular complications of diabetes through this chapter. The better understanding of epigenetic mechanisms and their role in diabetic microvascular complications could be used in clinical management of DN as well as DR or could

be helpful to improve the available therapies for these complications.

**Keywords:** diabetes, epigenetics, methylation, histone modification

Diabetes is a chronic metabolic disorder in which blood glucose levels upsurge more than normal. Type 2 diabetes mellitus (T2DM) contributes to the majority of diabetes cases accounting for more than 90% of them. An imbalance of insulin supply and demand results in type 2 diabetes [1]. Decrease in insulin sensitivity accompanied by deficiency of insulin are the two primary pathogenetic defects underlying type 2 diabetes and together explain 85–90% of diabetes [2]. Long term
